Clinical and experimental studies indicate that angiotensin II (A II) is involved in the process of tissue destruction in chronic renal diseases. Since the recognition of its potent vasoconstrictor action in the renal circulation. A II has several times come into the forefront in the scientists by revealing new biological actions which are apparently unrelated to any of its previously recognised actions. Many of these actions have now been extensively studied. Of interest, also, are its non-renal actions which are now known to be similarly rich in variety, due to extensive investigations on the central nervous and other organ systems.
Transgenic mice which overexpress growth hormone (GH) may be used a model system to examine growth, kidney pathology, as well as the medical condition known as acromegaly (hyper-growth hormone secretion). GH is a pleiotropic 22 kDa polypeptide hormone which elicits body growth in jeuvenille animals and also mediates protein, carbohydrate, and lipid metabolism. The structure / function relationships of selected residues of bovine (b) GH a-helix I were approached using site-directed mutagenesis in concert with the production of bGH analog transgenic mice. Phenyalanine (Phe, F) 11 and histidine (His, H) 22 in the amino-terminus of bGH were the targeted amino acids. bGH and the bGH analog transgenic mice all exhibited the enhanced growth phenotype similar to bGH transgenic mice and had elevated IGF-1 serum concentrations. However, bGH-H22R mice demonstrated levels of blood urea nitrogen (BUN) and serum creatinine (SCR) several fold higher than the other transgenic mice. Elevated BUN and SCR are an indication of renal insufficiency in this mouse line. Glucose tolerance testing in the bGH-H22R mice revealed that they possessed a lower tolerance for glucose, or an enhancement of the diabetogenic properties of the hormone as compared to wild-type and other GH analog transgenic mice: In addition to the glomerulosclerosis found in bGH mice, histological examination of the mature bGH-H22R mice demonstrated severe glomerulosclerosis, as well as cystic kidney lesions.
Complement is important to host defense and the regulation of inflammation. The liver is overwhelmingly the major source of circulating complement. However, many other organs are capable of synthesizing some or all of the complement components in a regulated tissue-specific manner. There is increasing evidence that this locally generated complement is biologically active and exerts powerful effects within the local environment. We review the role of local complement synthesis within different organs and speculate on its implication for immune and metabolic functions.
Carassius auratus gibelio was chosen as an organism with a high level of tolerance against heavy metal to investigate changes in monovalent ions content in its tissues. Fish were kept in 10 ppm Cu2+ (3h), CrO4 2- (96h), Co2+(96h), Pb2+ (8h) and control (96h) solutions, then tissues were dissected and prepared for X-ray microanalysis. K+, Na+ and Cl- concentration was measured and calculated. Short periods of time of fish acclimation to Cu2+ (3h) and Pb2+ (8h) caused fish to suffocate as a consequence of heavy metal ions binding to gill mucopolisaccharides. Cl- and Na+ content decreased after Cu2+ treatment in kidney cells and muscle fibers, and so did K+ concentration in gill cells in comparison to control. After that CrO4 2- ions acclimation changes in all tissues and in all measured ions were observed. Similar effects were observed in Co2+ ions treatment but not for muscle fibers. Pb2+ ions caused an elevation of Cl- and Na+ ions content in gill cells and muscle fibers but decreasing in liver and kidney cells in comparison to control. Changes in monovalent ions concentration are probably related to heavy metal ions influence on ionic pump activity, their interaction with metabolic enzymes, ATP production or membrane phospholipids.
Human blood group antigens (BGA) are genetically determined glycoproteins found in many cells and tissues of different mammals. Their major biological functions are still undefined. There are few investigations analysing the evolutionary aspect of BGA tissue ditribution. The present study is aimed at examining the expression of human A and B antigens in the kidney and lung of some free-living vertebrates. The biotin-streptavidin-peroxidase immunostaining system was applied on kidney and lung paraffin sections derived from free-living representatives of five different vertebrate classes. Excluding the possibility of any non-specific staining by the application of inhibition tests, A and B antigens were demonstrated most constantly in epithelial cells of renal and respiratory tubules. They were also detected in chondrocytes of fish gills, in some muscular and endothelial cells. Single erythrocytes showed a positive cytoplasmic staining only in some higher vertebrates. Human BGA seem to be conserved carbohydrate structures with biological functions probably related to cell integrity and differentiation.
Mammary gland-specific expression of human genes and secretion of human proteins into the milk of transgenic farm animals provides an important tool for manufacturing of many valuable pharmaceuticals. More recently, attention has focused on urine-based expression systems as a much more cost-effective technology. Successful application of this technology, however, requires the definition of several crucial regulatory elements that direct production of the protein into the urinary tract. To date, the 5? flanking region of either the uroplakin II (UPII) or uromodulin (THP) genes were used to drive the expression of heterologous proteins in the bladder or kidney epithelium of the transgenic mice, respectively. Herein, the progress and current limitations in this field are presented. Other currently known urine-specific protein genes are also described.
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